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David Fletcher, MD Department of Medicine University of Toronto

Complicated cases. David Fletcher, MD Department of Medicine University of Toronto. CASE 1 . 54 yr /o man HIV positive 8 yrs ago Tenofovir /FTC/RTV/ Atazanavir x 4 yrs Previously documented NNRTI resistance with Y181C, G190A,and mixed m184v/ wt CD4 320 HIV Viral Load<40. CASE 1 .

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David Fletcher, MD Department of Medicine University of Toronto

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  1. Complicated cases David Fletcher, MDDepartment of MedicineUniversity of Toronto

  2. CASE 1 • 54 yr/o man • HIV positive 8 yrs ago • Tenofovir/FTC/RTV/Atazanavirx 4 yrs • Previously documented NNRTI resistance with Y181C, G190A,and mixed m184v/wt • CD4 320 HIV Viral Load<40

  3. CASE 1 • Genotype 1a Hepatitis C biopsy proven cirrhosis • Compensated and clinically stable • Previous therapy in 2009 with Peg INF/1200mg RBV daily resulted in a null response by history from the patient

  4. CASE 1 Patient is interested in a retrial of therapy for Hepatitis C with the new direct acting antiviral agents • Would you offer treatment? • Chance of cure? • Which 3rd agent would you choose and why? • Does patient’s antiretroviral history play a role in 3rd agent choice? • Is there a role for a 4 week lead in here regardless of agent chosen and if so…why?

  5. CASE 1 It was decided to move forwards with Peg INF/ 1200mg RBV/Telaprevir • Is it necessary to change current ARVs? • Would it be necessary to change ARVs if Boceprevir was chosen?...to what?

  6. CASE 1 Peg INF/1200mg RBV/Telaprevir…no lead in performed • Week 0 HCVRNA 3.7 x 10e7 • Week 4 HCVRNA detectable but<12 • Would you continue? • Are you concerned about the result? • When would you do the next HCVRNA?

  7. CASE1 It was decided to continue with Peg INF/1200mg RBV/Telaprevir and HCVRNA rechecked • Week 0 HCVRNA 3.7 x 10e7 • Week 4 HCVRNA detectable but<12 • Week 6 HCVRNA <12 • Would you continue?

  8. CASE 1 Peg INF/1200mg RBV/Telaprevir • Week 0 HB 140 • Week 2 HB 125 • Week 4 HB 109 • Week 6 HB 99…symptomatic • How would you manage anemia?

  9. CASE 1 Peg INF/600mgRBV/Telaprevir • Week 0 HCVRNA 3.7 x 10e7 • Week 4 HCVRNA detectable but<12 • Week 6 HCVRNA <12 HB 99 (symptoms) • Week 8 HCVRNA <12 HB 98 (less symptomatic) • What would you do? • How would you further manage anemia

  10. CASE 1 Peg INF/600mg RBV/Telaprevir • Week 0 HCVRNA 3.7 x 10e7 • Week 4 HCVRNA detectable but<12 • Week 6 HCVRNA <12 • Week 8 HCVRNA <12 • Week 12 HCVRNA detectable but <12 HB 103 • What would you do? • When would you do your next HCVRNA?

  11. CASE 1 Peg INF/RBV re-increased to 1200mg • Week 0 HCVRNA 3.7 x 10e7 • Week 4 HCVRNA detectable but <12 • Week 8 HCVRNA <12 • Week 12 HCVRNA detectable but <12 • Week 14 HCVRNA <12 HB 101 • What would you do?

  12. CASE 1 Peg INF/1200mg RBV • Week 0 HCVRNA 3.7 x 10e7 • Week 4 HCVRNA detectable but<12 • Week 12 HCVRNA detectable but <12 • Week 14 HCVRNA <12 HB 101 • Week 24 HCVRNA <12 HB 105 • How much longer would you treat? • When would you do your next HCVRNA?

  13. CASE 1 Peg INF/1200mg RBV • Week 0 HCVRNA 3.7 x 10e7 • Week 4 HCVRNA detectable but <12 • Week 12 HCVRNA detectable but <12 • Week 24 HCVRNA <12 • Week 36 HCVRNA <12 • Week 48 HCVRNA <12 • Are we finished therapy?

  14. CASE 1 An additional 24 weeks of PEG INF/RBV (for a total of 72 weeks of therapy) was offered to the patient given the existence of cirrhosis and ?slow HCVRNA clearance as evidenced by a detectable HCVRNA at week 4 and 12 Week 12 and 24 HCVRNA post 72 weeks of therapy were undetectable!

  15. CASE 2 • 52 yo man • HIV positive 5 yrs ago • CAD with previous MI 3 yrs ago/Hypertensive/Hypothyroidism • Tenofovir/FTC/Raltegravir x 4 yrs • CD4 700 HIV Viral Load<40

  16. CASE 2 • Hypercholesterolemia and Hypertriglyceridemia on combination therapy with Atorvastatin 80mg/day and Fenofibrate 145mg/day • Hypertension controlled on Amlodipine 10mg/day • Hypothyroidism controlled on 0.125 mg L-Thyroxine

  17. CASE 2 • Genotype 1a chronic hepatitis C • Naïve to therapy • F2-3/4 scarring • Ready to start triple therapy with PEG INF/RBV/Boceprevir • Atorvastatin decreased to 40mg/day • Baseline HCVRNA 1.66X10E6

  18. CASE 2 • Week 0 HCVRNA 1.66x10E6 • Week 4 HCVRNA (lead in)2.37x 10E2 • Week 8 HCVRNA <12 • At week 10 begins to feel tired/weak/constipated/muscle cramping • TSH noted to be 18.91…L-T4 increased to 0.15mg/d in response

  19. CASE 2 • At week 11 notes increasingly prominent myalgias, more predominant post interferon injection but lasting all week long as opposed to a few hrs post injection, along with increasing weakness • Hb stable at 105g/l over last few weeks with RBV dose reduction to 600mg/d • AST noted to be increasing while ALT has been normalizing over the last few weeks…also increasing swelling of ankles • ?Cause…Hepatic Decompensation?

  20. CASE 2 • CK measured at 83,700 • BP noted to be low at 90/55 and swelling of ankles worsened now to mid calf…no ascites noted clinically • Cause?

  21. CASE 2 • Atorvastatin and Fenofibrate discontinued!!! • CK fell over the next few weeks as did AST • The symptomatic myalgias and weakness improved over the subsequent month • Amlodipine discontinued…BP normalized to 130/80 and ankle swelling disappeared over the next month

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